Case Report: Reemerging Paragonimiasis in Umphang District, Thailand

ABSTRACT. Paragonimiasis is a food-born zoonotic parasitosis caused by Paragonimus spp. Six cases of reemerging paragonimiasis within the Karan hill-tribe near the Thai–Myanmar border were evaluated to review clinical manifestations, predisposing factors, and treatment regimens. All patients tested positive for paragonimiasis eggs and presented with an array of symptoms, including chronic cough, hemoptysis, peripheral eosinophilia, and thoracic radiograph abnormalities. All fully recovered after a 2- to 5-day course of 75 to 80 mg/kg/day praziquantel. We conclude that paragonimiasis should be considered during differential diagnoses to promote early treatment and to prevent misdiagnosis of reemerging or sporadic cases. This applies particularly to endemic regions and high-risk groups known to habitually consume raw or undercooked intermediate or paratenic hosts.


Case 1.
A 3-year-old Karan boy was severely malnourished, anemic, and suffered from progressive dyspnea and abdominal distension after continually consuming mountain crabs. He had no history of contact TB; sputum, stool, and pleural fluid tested positive for Paragonimus eggs. The thoracic radiograph taken during initial onset ( Figure 1A) revealed haziness and minimal reticulonodular infiltration in the right middle lobe (RML). Abdominal ultrasound ( Figure 1B) confirmed marked ascites, hepatosplenomegaly, and pericardial effusion (0.68 cm). Decreased abdominal distension, pulmonary infiltration, and increased weight (4 kg) were observed ( Figure 1C) 14 days after hospitalization and treatment (Table 1).
Case 2. A 4-year-old Karan girl had tachycardia, tachypnea, and fine crepitation in her right lower lobe (RLL) after consuming mountain crabs from the river near her parents' rice fields. No prior history of fever, chest pain, or contact TB was reported, and sputum test was positive for Paragonimus eggs. Figure 1D illustrates her thoracic radiograph during initial onset, with reticulonodular infiltration in the RML. Figure 1E illustrates resolution of this infiltration 2 months after treatment (Table 1).
Case 3. A 10-year-old Karan boy presented with cough and progressive dyspnea. Three months earlier, he had dengue hemorrhagic fever. He denied contact TB and his parents denied habitual eating of raw food. A sputum sample tested positive for Paragonimus eggs. Figure 1F and G illustrates the presence of hyperdense pleural effusion, with some calcification and haziness of the RLL, respectively. Figure 1H shows the patient's thoracic radiograph after treatment (Table 1) during a 7-month follow-up, with decreased pleural effusion.
Case 4. A 55-year-old Karan woman had productive hemoptysis, fatigue, myalgia, and weight loss. She had no history of fever, chest pain, or contact TB. She did not consume raw mountain crabs, but did drink alcohol habitually. Her sputum sample was positive for Paragonimus eggs. Supplemental Figure 1 and Figure 1I illustrate her thoracic radiographs a year prior to admission and during the hospital visit, respectively, with visible nodular infiltration in the left hilar region. Figure 1J shows her thoracic radiograph after a 2-month follow-up, with decreased pulmonary infiltration within the left hilar region and no reported clinical symptoms.
Case 5. A 60-year-old Karan man had progressive productive coughing with brown-tinged sputum, and fine crepitation in the right upper lobe (RUL). He drank and smoked actively, but denied weight loss, contact TB, or consuming raw food habitually. His sputum smear was positive for Paragonimus eggs. A thoracic radiograph ( Figure 1K) revealed multiple reticulonodular and nodular infiltration in the RUL and left lower lobe, respectively. The patient refused further investigation to diagnose paragonimiasis from lung malignancy. A 2-month follow-up revealed decreased pulmonary infiltration in the RUL after treatment ( Figure 1L). Case 6. A 66-year-old Karan woman had a productive cough with hemoptysis, cachexia, and coarse precipitation in her right lung. She received treatment of her neurocysticercosis, diagnosed 3 months prior by brain computed tomography, and was on Dilantin for her seizures. She denied history of fever, contact TB, or raw food consumption. Her sputum smear was positive for Paragonimus eggs. Figure 1M demonstrates her chest radiograph, with reticular infiltration in the RML. After treatment, this infiltration receded ( Figure 1N).
Seven fresh-water mountain crabs ( Figure 2A) were collected around Lae-Tong-Ku waterfall in Myanmar. Metacercaria  ( Figure 2B and C) were identified using a stereomicroscope (340 magnification) after blending, and polymerase chain reaction confirmed their identities to be P. heterotremus and Paragonimus pseudoheterotremus. This, coupled with the sudden number of cases, prompted us to arrange health education sessions with patients, community leaders, and villagers to prevent reinfection and future outbreaks.

DISCUSSION
The incidence of paragonimiasis in Thailand has decreased during the past few decades. Yoonuan et al. 4 reported that 6.3% of villagers' sputum samples in Phitsanulok Province tested positive for Paragonimus eggs in the 1980 s, and none in 2005. However, the prevalence of metacercaria in intermediate hosts (i.e., freshwater crabs) remains high. 4,5,15 Consumption of reservoir hosts that feed on these infected intermediates, contamination during food preparation (i.e., hemolymph of crabs), or consumption of preserved crustacean-based products (i.e., pickled crabs and sauces) are possible reasons for how four of our patients who claimed not to consume raw crustaceans contracted paragonimiasis. 18 This may explain the sudden increase in cases reported in 2017.
Rapid resolution was observed upon treatment with praziquantel (PZQ), with an 86% to 100% cure rate for a 75-mg/kg/day, thrice daily 2-day course, and 100% for a 3-day course. 3,19 Dizziness, headache, and gastrointestinal distress are some possible side effects, 6 but none were observed in this study. All patients recovered completely, but cachexic patients required longer time frames to resolve complications. 3,9,14 This demonstrated the high efficacy of anthelmintic drugs toward treating paragonimiasis in Thai adults and children, 5,18 with no eggs detected in 2-month follow-ups. 1 This efficacy also highlights that the problem lies, not in treatment, but in misdiagnosis. In China, 69% to 89% of paragonimiasis cases were misdiagnosed between 2009 and 2019, 3,13,14,20 as is often the case for early stages of infection (asymptomatic presentations or nonspecific symptoms). This delays effective treatment and increases the risk of morbidities, debilitation, and life-threatening complications. [1][2][3]15 Many of our patients had their treatment delayed (1 month-1 year) as a result of misdiagnoses, allowing their condition to become severe (cases 1-3) or chronic (cases 2 and 5). Lack of awareness and access to medical care (i.e., low economic status or difficulty traveling) exacerbated this delay further. 5 Key presentations of paragonimiasis include chronic cough with hemoptysis, fever, pleural effusion with peripheral eosinophilia, and abnormal thoracic radiographs. 3,8,12,14,17,19 All our patients had at least one of the symptoms just listed, with the most common being abnormal thoracic findings and eosinophilia (range, 5-55%). Misdiagnosis can occur easily should deliberate tests for Paragonimus eggs not be performed. This is because these clinical presentations overlap with those of TB, which is also prevalent and endemic in Thailand. A presumptive diagnosis of pulmonary TB and empirical anti-TB is of general practice despite negative acid-fast bacilli sputum samples. Pleuropulmonary paragonimiasis needs to be included in clinicians' list of differential diagnoses, particularly in endemic regions, to address underreporting, prevent misdiagnosis, and ensure rapid treatment initiation. 6,10,13,17 Antibody detection is the most sensitive method of diagnosis, followed by egg detection in sputum then stool. However, serological methods cannot distinguish serum antibodies readily between past and present infections, which are known to persist even after anthelmintic treatments. 21 For patients with early-onset (asymptomatic), chronic (inactive), or ectopic paragonimiasis, eggs in clinical samples may not be demonstrable. 1,2,4,5,10,13,19 Immunodiagnostics are excellent tools to assist diagnoses. 13,19 All patients in our study had detectable levels of egg production in sputum, stool, and pleural samples. Further laboratory analyses (see Supplemental Methods) identified P. heterotremus species complex (P. heterotremus and P. pseudoheterotremus) from mountain crabs collected from Loy Tong Ku, the local waterfall, as the predominant etiological agents. This supports previous literature regarding high metacercaria prevalence in intermediate hosts.
Combined educational and preventive campaigns were proposed to address sporadic and reemerging cases of paragonimiasis. 15,18 In addition to increasing awareness in clinicians, medical outreach programs aimed toward educating local communities (particularly primary schools) would decrease cultural and habitual practices of consuming raw crustaceans and paratenic hosts. 3,4 One example is the mass screening and prevention campaigns put forth by Miyazaki, Japan's local government during the 1950 s and 1960 s, which reduced parasitosis prevalence significantly and prevented sporadic, reemerging cases. 6 All patients in our study received health education to prevent reinfection. Coupling this with continuous mass treatment, sanitary improvements, and quality control of food products, 9,13 would further regulate the number of cases in other endemic regions in Thailand (e.g., Phetchabun, Saraburi, Nakhon Nayok, Chiang Rai, Loei, Nan, Phitsanulok, and Mae Hong Son provinces). 4,5,9,11,22 To conclude, we assessed six cases of paragonimiasis in the Umphang District to remind clinicians of this endemic, reemerging, food-born parasitosis and prevent misdiagnosis.
Paragonimiasis should be included in the list of differential diagnoses to promote early treatment with PZQ, particularly for high-risk groups that habitually consume raw or undercooked intermediate or paratenic hosts, and present with chronic cough, hemoptysis, peripheral eosinophilia, and/or other thoracic radiograph abnormalities. Sputum, stool, and immunodiagnostic techniques can be coupled to confirm diagnosis.